We are studying the pharmacological aspects of ion and mucous secretion in the rat submandibular gland. Rat submandibular gland cells are isolated using a chromatographically purified collagenase and hyaluronidase and the pharmacological aspects of submandibular secretion is evaluated in terms of (1) the receptor mediated, physiological response to cholinergic and adrenergic agonists. This is accomplished by determining the net efflux of K and the amount of 14C-glucosamine labeled mucin released into the cell suspension media following parasympathomimetic and sympathomimetic stimulation. (2) The changes in the levels of cyclic AMP and cyclic GMP following stimulation are determined and then correlated with the receptor mediated, physiological response of these cells with and without the addition of phosphodiesterase inhibitors. The method developed for the isolation of rat submandibular cells results in the isolation of the principal secretory cells in their natural functional units and they demonstrate a high degree of sensitivity to various secretagogues tested. These studies are intended to improve our understanding of the membrane mediated and subsequent intracellular events that are thought to be important in the stimulus-secretion coupling mechanism in this gland.